Biomarkers for neurodegenerative diseases in regulatory decision-making by the European Medicines Agency

IF 4.9 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-03-27 DOI:10.1002/trc2.70072

Audrey M. M. Hermans, Elisabeth Bakker, Viktoriia Starokozhko, Loes den Otter, André J. A. Elferink, Angela Bradshaw, Lorenzo Guizzaro, Peter G. M. Mol, Anna M. G. Pasmooij

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引用次数: 0

Abstract

INTRODUCTION

Biomarkers (BMs) are valuable tools to facilitate early diagnosis of (subtypes of) diseases, improve patient selection and stratification, and detect therapeutic effects or safety concerns. This study explores the extent to which BMs are utilized in the development of treatments for neurodegenerative diseases (NDDs), as well as topics of discussion regarding BMs in regulatory advice- and decision-making processes and sharing of BM-related data.

METHODS

The European Medicines Agency's marketing authorization application (MAA), qualification (QA/QO), and scientific advice (SA) procedures regarding NDDs were screened, and those that mention BMs were analyzed. Data were extracted on the intended disease, BM type, and context of use proposed by applicants. BMs were categorized based on both nature and function.

RESULTS

In total, 105 procedures that discussed BMs were analyzed, 57 SAs (January 2020 to December 2022), 19 QAs/QOs (January 2008 to December 2023), and 29 MAAs (January 1995 to December 2023). The majority involved Alzheimer's disease (AD; n = 30), Parkinson's disease (PD; n = 9), and multiple sclerosis (MS; n = 33). Imaging BMs were the most common type of BMs discussed, and most BMs were used as pharmacodynamic/response measures. The acceptance and role of BMs differed between AD, PD, MS, and other NDDs. In regulatory procedures for AD, for example, diagnostic BMs guiding patient selection were commonly discussed, whereas in MAAs for MS, imaging BMs (particularly lesions) were generally accepted as supportive/secondary endpoints.

DISCUSSION

Despite the established role of certain BMs, mainly imaging BMs for MS, there remains a major need for more precise and reliable BMs to improve diagnostic accuracy and treatment monitoring for NDDs. To implement novel BMs and facilitate development of new treatments and to eventually improve clinical practice, robust evidence bases showcasing biological plausibility or clear clinical benefits are essential. Collaboration and data-sharing among stakeholders is vital in generating this evidence and enhancing the understanding and management of NDDs.

Highlights

The European Medicines Agency's marketing authorization applications and qualification and scientific advice procedures.
One hundred five procedures were analyzed regarding neurodegenerative diseases that discuss biomarkers.
We found that acceptance and role of biomarkers differ per disease.
Biological plausibility/clinical benefits are essential for biomarker implementation.

Abstract Image

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欧洲药品管理局监管决策中神经退行性疾病的生物标志物

生物标志物（BMs）是促进疾病（亚型）早期诊断、改善患者选择和分层、检测治疗效果或安全问题的有价值的工具。本研究探讨了脑转移在神经退行性疾病（ndd）治疗开发中的应用程度，以及关于脑转移在监管建议和决策过程中的讨论主题，以及脑转移相关数据的共享。方法筛选欧洲药品管理局有关ndd的上市许可申请（MAA）、鉴定（QA/QO）和科学建议（SA）程序，并对涉及脑转移瘤的程序进行分析。数据提取的预期疾病，BM类型和使用背景的申请人提出。脑转移是根据性质和功能进行分类的。结果共分析了105个讨论BMs的程序，57个sa（2020年1月至2022年12月），19个qa /QOs（2008年1月至2023年12月）和29个maa（1995年1月至2023年12月）。其中大多数涉及阿尔茨海默病(AD；n = 30)，帕金森病(PD；n = 9)，多发性硬化症(MS；n = 33)。影像学脑转移是讨论的最常见的脑转移类型，大多数脑转移被用作药效学/反应测量。脑转移瘤的接受程度和作用在AD、PD、MS和其他ndd之间存在差异。例如，在AD的监管程序中，通常会讨论诊断性脑转移引导患者选择，而在MS的MAAs中，成像脑转移（特别是病变）通常被接受为支持/次要终点。尽管某些脑转移的作用已经确立，主要是对多发性硬化症的脑转移成像，但仍然需要更精确和可靠的脑转移来提高ndd的诊断准确性和治疗监测。为了实施新的脑转移疗法，促进新疗法的发展，并最终改善临床实践，展示生物学合理性或明确临床益处的强有力的证据基础是必不可少的。利益攸关方之间的协作和数据共享对于产生这一证据和加强对ndd的理解和管理至关重要。重点介绍欧洲药品管理局的上市许可申请、资格和科学咨询程序。我们分析了讨论生物标志物的神经退行性疾病的105例手术。我们发现生物标志物的接受度和作用因疾病而异。生物学合理性/临床效益是生物标志物实施的关键。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

期刊介绍： Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.